Hyperalgesic pain conditions are conditions of heightened pain perception caused by tissue damage. These conditions are a natural response of the nervous system apparently designed to encourage protection of the damaged tissue by an injured individual, to give time for tissue repair to occur. The symptoms of hyperalgesic pain conditions include hyperalgesia, allodynia (tactile, thermal) and paresthesia. Hyperalgesia is an abnormal pain response to a pain stimulus. Allodynia is a condition where a normal stimulus causes pain. Paresthesia is an abnormal sensation of the skin such as numbness, tingling, pricking, burning, crawling with no objective cause. There are two known underlying causes of these conditions, an increase in sensory neuron activity, and a change in neuronal processing of nociceptive information which occurs in the spinal cord. These conditions can be debilitating in chronic inflammation and when sensory nerve damage has occurred (i.e. neuropathic pain). As mentioned above, hyperalgesic pain conditions are a consequence in most instances of tissue damage, either damage directly to a sensory nerve, or damage of the tissue innervated by a given sensory nerve.
Diseases involving damage to sensory nerves which contain a component of neuropathic pain include, but are not limited to, diabetic neuropathy, cancer pain, fibromyalgia, myofascial pain syndrome, osteoarthritis, pancreatic pain, pelvic/perineal pain, post-herpetic neuralgia, complex regional pain syndrome, sciatica/lumbar radiculopathy, spinal stenosis, temporo-mandibular joint disorder, HIV pain, trigeminal neuralgia, chronic neuropathic pain, lower back pain, failed back surgery pain, post-operative pain, post-physical trauma pain (including gunshot, RTA, burns), cardiac pain, chest pain, pelvic pain/pid, joint pain (tendonitis, bursitis, acute arthritis), neck pain, obstetric pain (labour/C-section), renal colic, acute herpes zoster pain, acute pancreatitis, breakthrough pain (cancer) and dysmenorhoea/endometriosis.
Two major classes of analgesics are known: (i) non-steroidal anti-inflammatory drugs (NSAIDs) and the related COX-2 inhibitors; and (ii) opiates based on morphine. Analgesics of both classes are reasonably effective in controlling normal, immediate or nociceptive pain. However, they are less effective against some types of hyperalgesic pain, such as neuropathic pain. Many medical practitioners are reluctant to prescribe opiates at the high doses required to affect neuropathic pain because of the side-effects caused by administration of these compounds, and the possibility that patients may become addicted to them. NSAIDs are much less potent than opiates, so even higher doses of these compounds are required. This is, however, undesirable because these compounds cause irritation of the gastro-intestinal tract.
There is, therefore, a need for anti-hyperalgesics and neuropathic pain treatments which are sufficiently potent to control pain perception in neuropathic and other hyperalgesic syndromes, and which do not have serious side-effects or cause patients to become addicted to them.
EP-A-0050671 describes thiazolo[3,2-a]pyrimidine derivatives of formula (I)
which exhibit immuno-regulating properties and are useful as agents for curing autoimmune diseases such as nephritis and rheumatoid arthritis. One particular compound of formula (I) is 6-(p-chlorobenzyl)-5H-2,3,6,7-tetrahydro-5,7-dioxothiazolo[3,2-a]pyrimidine, otherwise known as nuclomedone and hereinafter referred to as Compound 1, the chemical structure of which is:

Compound 1 was originally developed as a potential treatment for rheumatoid arthritis or nephritis, but has now been discontinued in these indications. In preclinical studies, nuclomedone restored kidney function in mice with autoimmune neuropathy and inhibited lipopolysaccharide-induced polyclonal antibody responses.